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Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant

FL. Braddock, JC. Gardner, N. Bhattacharyya, B. Sanchez-Pintado, M. Costa, C. Zarouchlioti, A. Szabo, P. Lišková, ME. Cheetham, RD. Young, C. Thaung, AE. Davidson, SJ. Tuft, AJ. Hardcastle

. 2024 ; 32 (12) : 1583-1589. [pub] 20240821

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25003301

Grantová podpora
Wellcome Trust - United Kingdom

E-zdroje Online Plný text

NLK Free Medical Journals od 2009
PubMed Central od 2009 do Před 1 rokem
Europe PubMed Central od 2009 do Před 1 rokem
ProQuest Central od 2000-01-01 do Před 1 rokem
Open Access Digital Library od 1998-01-01
Health & Medicine (ProQuest) od 2000-01-01 do Před 1 rokem

Odkazy

PubMed 39169229
DOI 10.1038/s41431-024-01687-8
Knihovny.cz E-zdroje

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue removed during surgery revealed mild stromal textural alterations with alcianophilic deposits. Whole genome sequence data were generated for four affected individuals. No rare variants (MAF < 0.001) were identified in established corneal dystrophy genes. However, a novel heterozygous missense variant in exon 4 of SPARCL1, NM_004684: c.334G > A; p.(Glu112Lys), which is predicted to be damaging, segregated with disease. SPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. Interestingly, SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Therefore, we performed immunohistochemistry to compare SPARCL1 and decorin localisation in corneal tissue from an affected family member and an unaffected control. Strikingly, the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium. In summary, we describe a novel autosomal dominant corneal stromal dystrophy associated with a missense variant in SPARCL1, extending the phenotypic and genetic heterogeneity of inherited corneal disease.

Citace poskytuje Crossref.org

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